Osteopontin stimulates invasion of NCI‐h295 cells but is not associated with survival in adrenocortical carcinoma |
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| Authors: | Dirk Weismann Juliane Briese Joscha Niemann Matthias Grüneberger Patrick Adam Stefanie Hahner Sarah Johanssen Wei Liu Shereen Ezzat Wolfgang Saeger Ana‐Maria Bamberger Martin Fassnacht Heinrich M Schulte Sylvia L Asa Bruno Allolio Christoph M Bamberger |
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| Affiliation: | 1. University Hospital of Würzburg, Department of Internal Medicine I, Endocrine and Diabetes Unit, Germany;2. These authors contributed equally to this study.;3. Department of Laboratory Medicine and Pathobiology, University of Toronto and Department of Pathology, University Health Network and Toronto Medical Laboratories, Canada;4. Institute of Molecular Medicine, University of Leeds, UK;5. Department of Obstetrics and Gynaecology, University of Greifswald, Germany;6. Laboratory of Endocrinology and Metabolism of Ageing, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany;7. University of Würzburg, Institute of Pathology, Germany;8. The Endocrine Oncology Site Group, Mount Sinai and Princess Margaret Hospitals, Toronto, Ontario, Canada;9. Institute for Pathology, Marienkrankenhaus Hamburg, Germany;10. Endokrinologikum Hamburg, Germany |
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| Abstract: | Gene array studies indicated that osteopontin (OPN) mRNA is highly expressed in adrenocortical carcinomas (ACCs). OPN enhances invasiveness, proliferation, and metastasis formation, and is associated with poor survival in some malignant diseases. Integrin αvβ3 has been shown to mediate OPN effects on invasion. In this study, we demonstrated OPN and integrin αvβ3 expression in normal adrenal glands and benign adenomas, with staining seen exclusively in adrenocortical cells as well as even stronger staining in ACC. Western blot analysis confirmed overexpression of OPN in ACC (p < 0.01). With Matrigel invasion assays, we have shown that OPN greatly stimulates the invasiveness of NCI‐h295 cells (>six‐fold increase, p < 0.001). Transfection with integrin αvβ3 further increased invasiveness after OPN stimulation (p < 0.001). This increase was reversed by the addition of an anti‐integrin β3 antibody, indicating a functional relationship of OPN and integrin αvβ3 in ACC. With tissue arrays, we confirmed high OPN expression in 147 ACC samples. However, no association with survival was seen in Kaplan‐Meier analysis including 111 patients with primary tumours graded for OPN staining and follow‐up data available. In conclusion, our in vitro data indicate that OPN and integrin αvβ3 may act as a functional complex facilitating the invasiveness of adrenocortical tumours. This relationship remains of relevance to our understanding of carcinogenesis, but further studies are needed to address the physiological and pathological function of OPN in adrenal tissue. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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| Keywords: | adrenocortical cancer osteopontin OPN proliferation invasion tissue microarray |
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